Skip Navigation

This Article
Right arrow Print PDF (3618K)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (51)
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Mori, K.
Right arrow Articles by Stein, C.A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mori, K.
Right arrow Articles by Stein, C.A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 1989, Vol. 17, No. 20 8207-8219
© 1989

CHEMISTRY

Phosphoroselenoate oligodeoxynucleotides: synthesis, physico-chemical characterization, anti-sense inhibitory properties and anti-HIV activity

K. Mori, C. Boiziau1, C. Cazenave1, M. Matsukura, C. Subasinghe, J.S. Cohen, S. Broder, J.J. Toulmé and C.A. Stein*

Medicine Branch and Clinical Onocology Program, National Cancer Institute, NIH Bethesda, MD 20892, USA 1Laboratoire de Biophysique, INSERM U201, CNRS UA 481, Muséum National d'Histoire Naturelle 43 rue Cuvier F-75231 Paris Cedex 5, France

*To whom correspondence should be addressed

Received June 2, 1989. Revised September 15, 1989. Accepted September 15, 1989.

Oligodeoxynucleotides with a phosphorus atom in which one of the non-bridging oxygen atoms is substituted by selenium were prepared and investigated with respect to their antisense properties. A general synthesis of phosphoroselenoate analogs of oligonucleotides is described using potassium selenocyanate as the selenium donor. The compounds, characterized by 31P NMR, were shown to decompose to phosphate with a half-life of ca. 30 days. Melting temperatures of duplexes between poly(rA) or poly(rI) with oligo(dT) and oligo(dC), respectively, indicate diminished hybridization capability of phosphoroselenoate oligomers relative to both the unmodified phosphodiester oligomers and the phosphorothioate congeners. A phosphoroselenoate 17-mer is a sequence specific inhibitor of rabbit ß-globin synthesis in wheat germ extract and in injected Xenopus oocytes. In contrast phosphoroselenoate analogs are potent non-sequence specific inhibitors in rabbit reticulocyte lysate. In vitro HIV assays were carried out on a phosphoroselenoate sequence and compared with a phosphorothioate analogue that has previously been shown to exhibit anti-HIV activity (Matsukura et al., Proc. Natl. Acad. Sci. (1987) 84, 7706–7710). The phosphoroselenoate was somewhat less active, and was much more toxic to the cells.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 ScienceHome page
C. Stein and Y. Cheng
Antisense oligonucleotides as therapeutic agents--is the bullet really magical?
Science, August 20, 1993; 261(5124): 1004 - 1012.
[Abstract] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.